PROTECT 1 clinical trial

The IND review is unique among the FDA s application review processes. In many respects, this process and the FDA s treatment of INDs represents a delicate balance between the federal government s responsibility to protect clinical trial subjects from unnecessary risks and its desire to avoid becoming an impediment to the advance of medical research. Given these dual goals, the FDA must perform a safety review of an IND prior to clinical trials, but has only 30 days in which to reach an initial determination on the filing. 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

Influenza. Although current influenza vaccine (subunit spHt vaccine) has been in use yearly for the elderly, it is not recommended for the general population or infants. Improvements to increase or prolong the immunogenicity, reduce the side-effects (due to egg production procedure), and provide mass protection are stiU being pursued. One approach is to use a five, attenuated vims though cold adaptation. A vaccine has been used in Russia and demonstrated to be safe and efficacious for infants (82). Clinical trials for a similar vaccine are being carried out in the United States (83). 

One of the early vaccine candidates was directed against sporo2oites, the form of the parasites that is first injected into the host by a mosquito. With recent development of recombinant techniques, several circumsporo2oite proteins or its related peptides were proposed as the vaccine candidates. Clinical trials have been carried out. The vaccines were immunogenic, but did not provide sufficient protective efficacy (90,91). 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Recent findings from the ATBC stndy even showed that P-carotene snpple-mentation increased the post-trial risk of a hrst-ever non-fatal MI. Two secondary prevention trials, the Heart Protection Stndy and the ATBC presented similar resnlts. The former showed no association between P-carotene and fatal or non-fatal vascular events and the latter reported signihcantly increased risks of fatal coronary events in the P-carotene-snpplemented gronp. Resnlts of clinical trials focused on the effects of carotenoids on CVD biomarkers are controversial. Although carotenoid supplementation increased sernm levels,only lycopene was shown to be inversely associated with lipid, protein, DNA and LDL oxidation, and plasma cholesterol levels. - - ... 

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